Tripodi 2018 Biochim Biophys Acta Mol Cell Res
|Tripodi F, Castoldi A, Nicastro R, Reghellin V, Lombardi L, Airoldi C, Falletta E, Maffioli E, Scarcia P, Palmieri L, Alberghina L, Agrimi G, Tedeschi G, Coccetti P (2018) Methionine supplementation stimulates mitochondrial respiration. Biochim Biophys Acta Mol Cell Res 1865:1901-13.|
Tripodi F, Castoldi A, Nicastro R, Reghellin V, Lombardi L, Airoldi C, Falletta E, Maffioli E, Scarcia P, Palmieri L, Alberghina L, Agrimi G, Tedeschi G, Coccetti P (2018) Biochim Biophys Acta Mol Cell Res
Abstract: Mitochondria play essential metabolic functions in eukaryotes. Although their major role is the generation of energy in the form of ATP, they are also involved in maintenance of cellular redox state, conversion and biosynthesis of metabolites and signal transduction. Most mitochondrial functions are conserved in eukaryotic systems and mitochondrial dysfunctions trigger several human diseases. By using multi-omics approach, we investigate the effect of methionine supplementation on yeast cellular metabolism, considering its role in the regulation of key cellular processes. Methionine supplementation induces an up-regulation of proteins related to mitochondrial functions such as TCA cycle, electron transport chain and respiration, combined with an enhancement of mitochondrial pyruvate uptake and TCA cycle activity. This metabolic signature is more noticeable in cells lacking Snf1/AMPK, the conserved signalling regulator of energy homeostasis. Remarkably, snf1Δ cells strongly depend on mitochondrial respiration and suppression of pyruvate transport is detrimental for this mutant in methionine condition, indicating that respiration mostly relies on pyruvate flux into mitochondrial pathways. These data provide new insights into the regulation of mitochondrial metabolism and extends our understanding on the role of methionine in regulating energy signalling pathways.
• Keywords: MPC (mitochondrial pyruvate carrier), Metabolomics, S-adenosyl-methionine, Saccharomyces cerevisiae, Shotgun proteomics, Snf1/AMPK • Bioblast editor: Plangger M • O2k-Network Lab: IT Bari Palmieri L
Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology
Organism: Saccharomyces cerevisiae
Preparation: Isolated mitochondria Enzyme: Inner mt-membrane transporter, TCA cycle and matrix dehydrogenases Regulation: Amino acid Coupling state: LEAK, OXPHOS Pathway: N, S HRR: Oxygraph-2k